Egg Allergens

Egg Proteins Overview

Egg White Allergens

Ovomucoid (Gal d 1)	Dominant allergen in egg white, possibly due to its stability In children, persistent egg allergy was associated with higher sIgE levels to ovomucoid than children who outgrew their egg allergy. Resolution was associated with the absence or decline in ovomucoid sIgE level. Gastric digestion can reduce the allergenicity of ovomucoid, which can explain why some patients have skin contact reactions to egg, but not ingestion reactions Heating may decrease allergenicity by blocking epitope access through interactions with the food matrix and causing conformational change that may decrease allergenicity Ovomucoid may predict outcome of baked egg challenges In one study with challenges to heated and unheated egg white powder, sIgE to ovomucoid >11 kU/L correlated with a high risk (95% specific) of reacting to heated (as well as raw) egg white, whereas a level <1 kU/L correlated with a low risk of reaction (95% sensitive) to heated egg white, even if the patient might react to raw egg white In a study with challenges to heated egg in muffin and waffle, ovomucoid sIgE level of 50 kU/L was more than 90% predictive, whereas an undetectable level of ovomucoid-specific IgE still carried a 10% chance of heated egg reactivity A lower ovomucoid sIgE/IgG4 ratio is associated with heated egg tolerance
Ovalbumin (Gal d 2)	Most abundant (54%) protein in egg white Heating may decrease allergenicity by blocking epitope access through interactions with the food matrix and causing conformational change that may decrease allergenicity A lower ovalbumin sIgE/IgG4 ratio is associated with heated egg tolerance
Ovotransferrin, also known as conalbumin (Gal d 3)	Role of sIgE antibody to ovotransferrin in the diagnosis of egg allergy has not been determined
Lysozyme (Gal d 4)	Commonly used as a food preservative and in some pharmaceuticals and foods (e.g. eye drops and cheese) therefore individuals sensitized to lysozyme may react when exposed to such products Considered an important occupational allergen, causing asthma via the inhalation route
Other Egg white cystatin Lipocalin-type prostaglandin D synthase (L-PGDS)	Recently identified allergen candidates, unclear clinical significance

Egg Yolk Allergens

Not a significant cause of egg allergy

Chicken serum albumin, also known as alpha-livetin (Gal d 5)	Bird-egg syndrome Primary sensitization to chicken serum albumin (feathers, serum, droppings, and meat) resulting in food allergy to serum albumin in egg yolk Only a minority of patients with bird feather allergy report chicken meat allergy likely because the allergen is altered by cooking Most frequently observed in individuals with frequent exposure to birds (bird fanciers, etc.)
Other Vitellenin (apovitellenin I) Apoprotein B (apovitellenin VI)	Other egg yolk allergens with unclear clinical significance

Egg Allergen Cross-reactivity

Egg Allergy Phenotypes

Patients with IgE against sequential epitopes tend to have persistent allergy, whereas those with IgE against conformational epitopes tended to have transient allergy
Majority (74%) of children with egg allergy tolerate extensively heated egg (e.g. muffin and waffle made with eggs), and tolerance is gained twice as rapidly to well-cooked egg than uncooked egg (median age resolution 5.6 years vs. 10.3)
Low ovomucoid sIgE may predict tolerance of heated egg
Low ovomucoid and ovalbumin sIgE/IgG4 ratios are associated with heated egg tolerance
Higher egg white sIgE level is associated with persistent baked and regular egg reactivity, while initial baked egg reactivity is not

Diagnosis

Skin prick test
Specific IgE
- Tests available from Phadia
  - Complete allergen
    - Egg white
    - Egg yolk
  - Component resolved diagnostics
    - Ovomucoid (nGal d 1)
    - Ovalbumin (nGal d 2)
    - Ovotransferrin/conalbumin (nGal d 3)
- Performance of egg white sIgE in predicting baked egg OFC in a retrospective study of 100 children (anaphylaxis to egg within 2 years or convincing reaction to baked egg within 6 months excluded). No difference in egg white skin test size (median 7 mm) between OFC pass/fail groups.

Specific IgG4
- Ovalbumin and ovomucoid specific IgG4 may be useful when interpreted as IgE/IgG4 ratios (see above)

Statistical model using IgE and IgG4 levels

A statistical model including ovalbumin and ovomucoid IgE and IgG4 levels was superior to IgE alone in predicting outcome of heated egg challenge
Equation: 1/(1+exp(-2.33 + 0.26(sIgE OVA) + 0.19(sIgE to OVM) - 0.18(sIgG4 to OVA) + 0.99(sIgG4 to OVM) - 0.12(sIgE to OVA x sIgG4 to OVA) - 0.34(sIgE to OVM x sIgG4 to OVM)))
- If egg white sIgE <7 and if statistical model
  - >0.18, 47% with positive baked egg challenge
  - <0.18, 7-8% with positive baked egg challenge
- If egg white sIgE >7 and if statistical model
  - >0.18, 85% with positive baked egg challenge
  - <0.18, 100% with positive baked egg challenge

Oral food challenge

Egg Allergy Monitoring

Egg Allergy Natural Course

Egg Ladder

Resolution of egg allergy tends to occurs in stages starting with tolerance to well-cooked egg (e.g. cake), then lightly cooked egg (e.g. scrambled) followed finally by raw egg

Egg OFC Protocols

HealthNuts

Designed for 1 year old infant
Challenge material: egg white from 60 g free-range hen's egg. After the initial dose, the allergen is mixed with an age-appropriate previously tolerated food (eg, apple sauce or yogurt) on the basis of preferred parental choice of food.
Interval: 15 min
- Drop inside lip (not to touch outside lip)
- 0.5 mL
- 1 mL
- 2 mL
- 5 mL
- 10 mL
- Remainder of the 60 g egg white (usually 10-13 mL)